Immune-mediated pulmonary fibrosis occurs in patients with diffuse lung diseases such as hypersensitivity pneumonitis (HP). The mechanism(s) by which chronic inflammation causes lung fibrosis is poorly understood. In addition, there are no effective therapies that prevent development or arrest progression of fibrotic lung disease. HP is a T cell-mediated inflammatory lung disease caused by repeated exposure to an inhaled antigen such as mammalian proteins, bacteria and fungi and is the prototypical example of chronic lung inflammation resulting in fibrosis. Fibrotic lung disease occurs in up to 41% of patients with HP resulting in irreversible pulmonary dysfunction and a median survival of 7.1 years. Interestingly, patients with pulmonary fibrosis related to HP tend to be older (Mean: 61 years-old) than non-fibrotic patients (Mean: 52 years-old) suggesting that older patients may be at increased risk of developing fibrotic lung disease caused by chronic exposure to inhaled antigens. We developed a murine model of HP to study the role of different T cell subsets in the generation of immune-mediated pulmonary fibrosis. In this model, ?? T cells reduce lung inflammation and subsequent fibrosis by limiting the expansion of pro-fibrotic CXCR3-expressing CD4+ T cells caused by repeated exposure to the ubiquitous environmental microorganism, Bacillus subtilis. We identified IL22 expression as a critical mechanism by which ?? T cells reduce B. subtilis-induced disease. Mice transgenic for ?? T cells and wild-type C57BL/6 mice have large expansions of IL22-expressing ?? T lymphocytes in the lung resulting in decreased inflammation and fibrosis. In the absence of ?? T cells and thus, reduced levels of IL22, TCR?-/- mice have increased cellular infiltrates and accelerated lung fibrosis. In the absence of CXCR3 expression by CD4+ T cells, CXCR3-/- mice have less collagen deposition in the lung in response to chronic exposure to inhaled B. subtilis. Reconstitution of TCR?-/-?-/- mice with CD4+CXCR3+ T cells followed by repeated inhalation of B. subtilis resulted in increased lung fibrosis relative to TCR?-/-?-/- mice reconstituted with CD4+CXCR3- T cells while TCR?-/-?-/- mice repeatedly exposed to inhaled B. subtilis in the absence of T cells did not develop significant inflammation or fibrosis. Collectively, these data suggest that CD4+CXCR3+ T cells are important in the pathogenesis of B. subtilis-induced pulmonary fibrosis. Since older individuals are at risk for developing lung fibrosis in HP, we will test the hypothesis that older mice will develop increased pulmonary fibrosis after chronic exposure to inhaled B. subtilis due to a lack of expansion of anti-inflammatory ?? T cells that results in further expansion of pro-fibrotic CD4+CXCR3+ T cells.